ABSTRACT OF THE DOCTORAL THESIS BY PILAR MARTÍNEZ HERAS
Thesis submitted by: PILAR MARTÍNEZ HERAS
Thesis title: SERUM CONCENTRATIONS AND APO E GENOTYPES IN THE ALZHEIMER DISEASE.
Thesis Advisor: LLUIS MASANA I MARIN
Department responsible for the Thesis: DEPARTMENT DE MEDICINA I CURUGÍA
ABSTRACT Contributions and new knowledge the thesis brings forward Alzheimers disease (AD) is a neurodegenerative process which is characterized for presenting a progressive and irreversible loss of the cognitive function. The clinical diagnosis is based on a neurological test and the exclusion of other dementia causes. The laboratory studies like thyroid function and vitamin B 12, and neuroimaging help to exclude other causes of cognitive impairment, but specific diagnosis tests do not exist for this disease, except for anatomopathological confirmation. To establish the diagnosis of AD new biomarkers are investigated, and up to now none have been recommended as diagnosis criteria. Age is the most important known risk factor for Alzheimers disease, but undoubtedly the most significant finding in the pathogenesis of AD has been the increase in the frequency of the allele E4 of the Apo E. The genetic characterization of Apo E determines serum Apo E concentrations in a high percentage. Therefore, our hypothesis is that the serum Apo E concentrations, brought about to a certain extent by the Apo E genotype, may determine the onset of AD and modify its clinical presentation.The relevance of this thesis is that it establishes the relation between serum ApoE concentrations and AD, as well as its relation with the Apo E genotype. It also rates the relation between neurological symptoms of AD, serum Apo E concentrations and the distinct genotypes.
Methodology used and more relevant conclusions
A case-control study was conducted in Sant Joan de Reus Hospital and Mora dEbre Hospital on 93 patients diagnosed of AD and 96 controls, which was carried out in cooperation with the ApoEurope project, a multicentric study coordinated by Nancy (France), in which 9 European countries took part. An interview with the patients was carried out including medical history, physical examination, Mini cognoscitive test (MEC) and a blood test including: determination of serum and erythrocyte folate, vitamin B12, CRP, TSH, T4, total cholesterol, HDL cholesterol, triglycerides, serum Apo E concentrations and Apo E genotype.
The main conclusions of this thesis are:
AD is related to low serum Apo E concentrations.
Low serum Apo E concentrations are related to each of the neurological symptoms of AD and with less than 23 points in the MEC test.
The presence of the Apo E4 genotype and being over 70 years old multiplies the probability of suffering from AD.
The E4 allele shows a clear association with lower punctuation in MEC and higher cognitive impairment.
It exists a strong association between the distinct genotypes Apo E and serum Apo E concentrations, with numbers significantly higher in E2 subjects and lower in E4.
Tangible results in the investigation: books, articles, communications and congresses
During the writing of this thesis two communications have been given on Congresses on Internal Medicine.
-Serum ApoE concentrations and ApoE genoptype in Alzheimer Disease. APOEUROPE study.
P. Martínez Heras, JM. Olivé, A. Martín, M. Heras, S. Olivé, G. Siest*, Ll. Masana. Servicio Medicina Interna, Hospital Universitari Sant Joan de Reus. *Centre de Médecine Préventive, Nancy. Francia.
Oral communication given in the 8th Congrés Catalá de Medicina Interna, 12-15 May 1999.
- Apo E4 genotype and serum Apo E concentrations in Alzheimer disease .
P. Martínez Heras, J. Velilla Marco, L. Masana, P. Figueras, M. Pérez Conesa, S. Terraza, J. Aguirre.
Oral Communication given in the XXVIIi National Congress of the Spanish Society of Internal Medicine. 21-24 November 2007, Sitges.